Developmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USA.
Developmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USA.
Cell Rep. 2021 Jul 6;36(1):109335. doi: 10.1016/j.celrep.2021.109335.
Virgin females of many species conduct distinctive behaviors, compared with post-mated and/or pregnant individuals. In Drosophila, this post-mating switch is initiated by seminal factors, implying that the default female state is virgin. However, we recently showed that loss of miR-iab-4/8-mediated repression of the transcription factor Homothorax (Hth) within the abdominal ventral nerve cord (VNC) causes virgins to execute mated behaviors. Here, we use genomic analysis of mir-iab-4/8 deletion and hth-microRNA (miRNA) binding site mutants (hth[BSmut]) to elucidate doublesex (dsx) as a critical downstream factor. Dsx and Hth proteins are highly complementary in CNS, and Dsx is downregulated in miRNA/hth[BSmut] mutants. Moreover, virgin behavior is highly dose sensitive to developmental dsx function. Strikingly, depletion of Dsx from very restricted abdominal neurons (SAG-1 cells) abrogates female virgin conducts, in favor of mated behaviors. Thus, a double-negative regulatory pathway in the VNC (miR-iab-4/8 ˧ Hth ˧ Dsx) specifies the virgin behavioral state.
与交配后和/或怀孕的个体相比，许多物种的处女雌性会表现出独特的行为。在果蝇中，这种交配后转变是由精液因子引发的，这意味着默认的雌性状态是处女。然而，我们最近发现，缺失 miR-iab-4/8 对转录因子 Homothorax (Hth) 的抑制作用，会导致腹部腹神经索（VNC）中的个体表现出交配行为。在这里，我们通过对 mir-iab-4/8 缺失和 hth-miRNA（miRNA）结合位点突变体（hth[BSmut]）的基因组分析，阐明 doublesex (dsx) 是一个关键的下游因子。dsx 和 Hth 蛋白在中枢神经系统中高度互补，并且 miRNA/hth[BSmut]突变体中的 Dsx 水平下调。此外，处女行为对发育中的 dsx 功能非常敏感。引人注目的是，从非常局限的腹部神经元（SAG-1 细胞）中耗尽 Dsx 会消除雌性的处女行为，转而表现出交配行为。因此，VNC 中的双负调控途径（miR-iab-4/8 上调 Hth 上调 Dsx）决定了处女的行为状态。
